Generating the Baryon Asymmetry of the Universe in Split Fermion Models

The origin of the matter-antimatter asymmetry of the universe is one of the major unsolved problems in cosmology and particle physics. In this paper, we investigate the recently proposed possibility that split fermion models -- extra dimensional models where the standard model fermions are localized to different points around the extra dimension -- could provide a means to generate this asymmetry during the phase transition of the localizing scalars. After setting up the scenario that we consider, we use a single fermion toy model to estimate the reflection coefficients for scattering off the phase boundary using a more realistic scalar profile than previous work resulting in a different Kaluza Klein spectrum. The value we calculate for $n_B/s$ is consistent with the mechanism being the source of the baryon asymmetry of our universe provided the $B-L$ violating processes have an efficiency of order $10^{-5}$.Comment: 17 pages, 3 figures; References added; Minor changes, Accepted for publication in Phys. Rev.

Suppressing Proton Decay By Separating Quarks And Leptons

Arkani-Hamed and Schmaltz (AS) have shown that proton stability need not originate from symmetries in a high energy theory. Instead the proton decay rate is suppressed if quarks and leptons are spatially separated in a compact extra dimension. This separation may be achieved by coupling five dimensional fermions to a bulk scalar field with a non-trivial vacuum profile and requires relationships between the associated quark and lepton Yukawa couplings. We hypothesise that these relationships are the manifestation of an underlying symmetry. We further show that the AS proposal may suggest that proton stability \emph{is} the result of an underlying symmetry, though not necessarily the traditional baryon number symmetry.Comment: 4 pages, references added to match published versio

Quark-Lepton Symmetry In Five Dimensions

We construct a complete five dimensional Quark-Lepton symmetric model, with all fields propagating in the bulk. The extra dimension forms an $S^1/Z_2\times Z_2'$ orbifold with the zero mode fermions corresponding to standard model quarks localised at one fixed point. Zero modes corresponding to left(right)-chiral leptons are localised at (near) the other fixed point. This localisation pattern is motivated by the symmetries of the model. Shifting the right-handed neutrinos and charged leptons slightly from the fixed point provides a new mechanism for understanding the absence of relations of the type $m_e=m_u$ or $m_e=m_d$ in Quark-Lepton symmetric models. Flavour changing neutral currents resulting from Kaluza Klein gluon exchange, which typically arise in the quark sector of split fermion models, are suppressed due to the localisation of quarks at one point. The separation of quarks and leptons in the compact extra dimension also acts to suppress the proton decay rate. This permits the extra dimension to be much larger than that obtained in a previous construct, with the bound $1/R\gtrsim30$ TeV obtained.Comment: 12 pages, references added to match published versio

The structure of Serratia marcescens Lip, a membrane-bound component of the type VI secretion system

The high-resolution crystal structure of S. marcescens Lip reveals a new member of the transthyretin family of proteins. Lip, a core component of the type VI secretion apparatus, is localized to the outer membrane and is positioned to interact with other proteins forming this complex system

Structural basis for type VI secreted peptidoglycan DL-endopeptidase function, specificity and neutralization in <em>Serratia marcescens</em>

Some Gram-negative bacteria target their competitors by exploiting the type VI secretion system to extrude toxic effector proteins. To prevent self-harm, these bacteria also produce highly specific immunity proteins that neutralize these antagonistic effectors. Here, the peptidoglycan endopeptidase specificity of two type VI secretion-system-associated effectors from Serratia marcescens is characterized. These small secreted proteins, Ssp1 and Ssp2, cleave between γ-d-glutamic acid and l-meso-diaminopimelic acid with different specificities. Ssp2 degrades the acceptor part of cross-linked tetratetrapeptides. Ssp1 displays greater promiscuity and cleaves monomeric tripeptides, tetrapeptides and pentapeptides and dimeric tetratetra and tetrapenta muropeptides on both the acceptor and donor strands. Functional assays confirm the identity of a catalytic cysteine in these endopeptidases and crystal structures provide information on the structure–activity relationships of Ssp1 and, by comparison, of related effectors. Functional assays also reveal that neutralization of these effectors by their cognate immunity proteins, which are called resistance-associated proteins (Raps), contributes an essential role to cell fitness. The structures of two immunity proteins, Rap1a and Rap2a, responsible for the neutralization of Ssp1 and Ssp2-like endopeptidases, respectively, revealed two distinct folds, with that of Rap1a not having previously been observed. The structure of the Ssp1–Rap1a complex revealed a tightly bound heteromeric assembly with two effector molecules flanking a Rap1a dimer. A highly effective steric block of the Ssp1 active site forms the basis of effector neutralization. Comparisons with Ssp2–Rap2a orthologues suggest that the specificity of these immunity proteins for neutralizing effectors is fold-dependent and that in cases where the fold is conserved sequence differences contribute to the specificity of effector–immunity protein interactions

The genus Serratia revisited by genomics

The genus Serratia has been studied for over a century and includes clinically-important and diverse environmental members. Despite this, there is a paucity of genomic information across the genus and a robust whole genome-based phylogenetic framework is lacking. Here, we have assembled and analysed a representative set of 664 genomes from across the genus, including 215 historic isolates originally used in defining the genus. Phylogenomic analysis of the genus reveals a clearly-defined population structure which displays deep divisions and aligns with ecological niche, as well as striking congruence between historical biochemical phenotyping data and contemporary genomics data. We highlight the genomic, phenotypic and plasmid diversity of Serratia, and provide evidence of different patterns of gene flow across the genus. Our work provides a framework for understanding the emergence of clinical and other lineages of Serratia

A holin and an endopeptidase are essential for chitinolytic protein secretion in <i>Serratia marcescens</i>

Pathogenic bacteria adapt to their environment and manipulate the biochemistry of hosts by secretion of effector molecules. Serratia marcescens is an opportunistic pathogen associated with healthcare-acquired infections and is a prolific secretor of proteins, including three chitinases (ChiA, ChiB, and ChiC) and a chitin binding protein (Cbp21). In this work, genetic, biochemical, and proteomic approaches identified genes that were required for secretion of all three chitinases and Cbp21. A genetic screen identified a holin-like protein (ChiW) and a putative l-alanyl-d-glutamate endopeptidase (ChiX), and subsequent biochemical analyses established that both were required for nonlytic secretion of the entire chitinolytic machinery, with chitinase secretion being blocked at a late stage in the mutants. In addition, live-cell imaging experiments demonstrated bimodal and coordinated expression of chiX and chiA and revealed that cells expressing chiA remained viable. It is proposed that ChiW and ChiX operate in tandem as components of a protein secretion system used by gram-negative bacteria

VgrG and PAAR Proteins Define Distinct Versions of a Functional Type VI Secretion System

The Type VI secretion system (T6SS) is widespread among bacterial pathogens and acts as an effective weapon against competitor bacteria and eukaryotic hosts by delivering toxic effector proteins directly into target cells. The T6SS utilises a bacteriophage-like contractile machinery to expel a puncturing device based on a tube of Hcp topped with a VgrG spike, which can be extended by a final tip from a PAAR domain-containing protein. Effector proteins are believed to be delivered by specifically associating with particular Hcp, VgrG or PAAR proteins, either covalently ('specialised') or non-covalently ('cargo' effectors). Here we used the T6SS of the opportunistic pathogen Serratia marcescens, together with integratecd genetic, proteomic and biochemical approaches, to elucidate the role of specific VgrG and PAAR homologues in T6SS function and effector specificity, revealing new aspects and unexpected subtleties in effector delivery by the T6SS. We identified effectors, both cargo and specialised, absolutely dependent on a particular VgrG for delivery to target cells, and discovered that other cargo effectors can show a preference for a particular VgrG. The presence of at least one PAAR protein was found to be essential for T6SS function, consistent with designation as a 'core' T6SS component. We showed that specific VgrG-PAAR combinations are required to assemble a functional T6SS and that the three distinct VgrG-PAAR assemblies in S. marcescens exhibit distinct effector specificity and efficiency. Unexpectedly, we discovered that two different PAAR-containing Rhs proteins can functionally pair with the same VgrG protein. Showing that accessory EagR proteins are involved in these interactions, native VgrG-Rhs-EagR complexes were isolated and specific interactions between EagR and cognate Rhs proteins identified. This study defines an essential yet flexible role for PAAR proteins in the T6SS and highlights the existence of distinct versions of the machinery with differential effector specificity and efficiency of target cell delivery